Figure 7
Figure 7. Effect of 15H8 on platelet and fibrin deposition in a baboon arteriovenous shunt thrombosis model. Thrombogenic devices depicted in Figure 2 were inserted into femoral arteriovenous shunts in olive baboons as described.9,13,14 Flow through the grafts was maintained at 100 mL per minute, producing an initial average wall shear rate of 265 s−1 within the 4-mm diameter portions of the graft. (A) Platelet accumulation in the collagen-coated, silicon linker, and silicon expansion chamber segments of grafts was assessed in real time by imaging of local 111In-labeled platelet accumulation using a GE-400T camera with NuQuest InteCam. The curves composed of closed circles (●) with error bars (±1 SD) represent mean values for 9 devices inserted into arterio-venous shunts in 2 untreated animals (control results). Individual results for 4 devices tested in the same 2 animals at least 1 hour after administration of anti-fXII antibody 15H8 (5-6 mg/kg IV) are indicated by the symbols ○, △, ▽, and ♢. (B) Endpoint determinations of total 125I-labeled fibrin deposition during the experiments in panel A. Fibrin deposition in the collagen-coated graft segment (left panel) and silicon expansion chamber (right panel) were determined for 8 of the 9 devices inserted before animals received 15H8 (●) and for the 4 devices tested after animals received 15H8 (○). Large bars indicate mean values and smaller bars ± 1 SD (C) Plasma TAT complex measured in blood obtained at various times after graft insertion from the arteriovenous shunt upstream of the site of graft insertion for 6 of 8 control grafts (●), and the 4 grafts placed after 15H8 administration (○). Large bars indicate mean values and smaller bars ± 1 SD.

Effect of 15H8 on platelet and fibrin deposition in a baboon arteriovenous shunt thrombosis model. Thrombogenic devices depicted in Figure 2 were inserted into femoral arteriovenous shunts in olive baboons as described.9,13,14  Flow through the grafts was maintained at 100 mL per minute, producing an initial average wall shear rate of 265 s−1  within the 4-mm diameter portions of the graft. (A) Platelet accumulation in the collagen-coated, silicon linker, and silicon expansion chamber segments of grafts was assessed in real time by imaging of local 111In-labeled platelet accumulation using a GE-400T camera with NuQuest InteCam. The curves composed of closed circles (●) with error bars (±1 SD) represent mean values for 9 devices inserted into arterio-venous shunts in 2 untreated animals (control results). Individual results for 4 devices tested in the same 2 animals at least 1 hour after administration of anti-fXII antibody 15H8 (5-6 mg/kg IV) are indicated by the symbols ○, △, ▽, and ♢. (B) Endpoint determinations of total 125I-labeled fibrin deposition during the experiments in panel A. Fibrin deposition in the collagen-coated graft segment (left panel) and silicon expansion chamber (right panel) were determined for 8 of the 9 devices inserted before animals received 15H8 (●) and for the 4 devices tested after animals received 15H8 (○). Large bars indicate mean values and smaller bars ± 1 SD (C) Plasma TAT complex measured in blood obtained at various times after graft insertion from the arteriovenous shunt upstream of the site of graft insertion for 6 of 8 control grafts (●), and the 4 grafts placed after 15H8 administration (○). Large bars indicate mean values and smaller bars ± 1 SD.

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